Genetic factors associated with elevation of uric acid after treatment with thiazide-like diuretic in patients with essential hypertension,Hypertension Research

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Genetic factors associated with elevation of uric acid after treatment with thiazide-like diuretic in patients with essential hypertension
Hypertension Research ( IF 4.3 ) Pub Date : 2019-11-20 , DOI: 10.1038/s41440-019-0356-x
Yuko Ohta _{1,

2} , Kei Kamide _{1,

3} , Hironori Hanada ₄ , Shigeto Morimoto ₅ , Takeshi Nakahashi ₅ , Shin Takiuchi ₆ , Toshihiko Ishimitsu ₇ , Takuya Tsuchihashi ₈ , Masayoshi Soma ₉ , T Tomohiro Katsuya ₁₀ , Ken Sugimoto ₁₀ , Hiromi Rakugi ₁₀ , Takafumi Oukura ₁₁ , Jitsuo Higaki ₁₁ , Hideo Matsuura ₁₂ , Tatsuo Shinagawa ₁₃ , Yosikazu Miwa ₁₄ , Toshiyuki Sasaguri ₁₄ , Michiya Igase ₁₅ , Tetsuro Miki ₁₅ , Kazuo Takeda ₁₆ , Katsuhiro Higashiura ₁₇ , Kazuaki Shimamoto ₁₇ , Ritsuko Katabuchi ₁₈ , Michio Ueno ₁₈ , Naonaga Hosomi ₁₉ , Johji Kato ₂₀ , Norio Komai ₂₁ , Shunichi Kojima ₂₂ , Kazuhiro Sase ₂₃ , Yoshio Iwashima ₁ , Fumiki Yoshihara ₁ , Takeshi Horio ₁ , Satoko Nakamura ₁ , Hajime Nakahama ₁ , Toshiyuki Miyata ₄ , Yuhei Kawano ₁

Affiliation

Division of Hypertension and Nephrology, National Cerebral and Cardiovascular Center, Osaka, Japan.
Department of General Internal Medicine, Kyushu Dental University, Fukuoka, Japan.
Division of Health Sciences, Osaka University Graduate School of Medicine, Osaka, Japan.
Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan.
Department of Geriatric Medicine, Kanazawa Medical University, Ishishikawa, Japan.
Department of Cardiology, Higashi-Takarazuka Satoh Hospital, Hyogo, Japan.
Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Tochigi, Japan.
Steel Memorial Yawata Hospital, Fukuoka, Japan.
Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Department of Integrated Medicine and Informatics, University Graduate School of Medicine, Ehime, Japan.
Saiseikai Kure Hospital, Hiroshima, Japan.
Japanese Red Cross Nagasaki Atomic Bomb Hospital, Nagasaki, Japan.
Departments of Clinical Pharmacology, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
Geriatric Medicine, Ehime University Graduate School of Medicine, Ehime, Japan.
Kyotokojohokenkai Hospital, Kyoto, Japan.
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Hokkaido, Japan.
National Fukuoka-Higashi Medical Center, Fukuoka, Japan.
Department of Neurology, Hiroshima University Graduate School of Medicine, Hiroshima, Japan.
Frontier Science Research Center, University of Miyazaki, Miyazaki, Japan.
Division of Nephrology, Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan.
National Hospital Organization Shizuoka Medical Center, Shizuoka, Japan.
Clinical Pharmacology, Juntendo University, Tokyo, Japan.

We investigated changes in blood pressure (BP) and metabolic adverse effects, especially elevation of uric acid (UA), after treatment with a thiazide-like diuretic (TD) in patients with essential hypertension. Furthermore, the role of genetic factors in the elevation of UA by TD was assessed by a 500 K SNP DNA microarray. The subjects included 126 hypertensive patients (57 women and 69 men, mean age 59 ± 12 years) who registered for the GEANE (Gene Evaluation for ANtihypertensive Effects) study. After one month of the nontreatment period, TD, indapamide, angiotensin II receptor antagonist valsartan, and Ca channel blocker amlodipine were administered to all patients for 3 months each in a randomized crossover manner. BP, renal function, serum UA level, and electrolytes were measured at baseline and at the end of each treatment period. Single nucleotide polymorphisms (SNPs) associated with UA elevation after treatment with indapamide were investigated by a genome-wide association study (GWAS). Indapamide significantly decreased both office and home BP levels. Treatment with indapamide also significantly reduced the estimated glomerular filtration rate and serum potassium and increased serum UA. Patients whose UA level increased more than 1 mg/dl showed significantly higher baseline office SBP and plasma glucose and showed greater decline in renal function compared with those who showed less UA increase (<1 mg/dl). Some SNPs strongly associated with an increase in UA after treatment with indapamide were identified. This study is the first report on SNPs associated with UA elevation after TD treatment. This information may be useful for the prevention of adverse effects after treatment with TD.

中文翻译：

原发性高血压患者噻嗪样利尿剂治疗后尿酸升高的相关遗传因素

我们调查了原发性高血压患者在用噻嗪样利尿剂 (TD) 治疗后血压 (BP) 和代谢不良反应的变化，尤其是尿酸 (UA) 升高。此外，遗传因素在 TD 引起的 UA 升高中的作用通过 500 K SNP DNA 微阵列进行评估。受试者包括注册 GEANE（抗高血压效应基因评估）研究的 126 名高血压患者（57 名女性和 69 名男性，平均年龄 59 ± 12 岁）。非治疗期 1 个月后，所有患者均以随机交叉方式给予 TD、吲达帕胺、血管紧张素 II 受体拮抗剂缬沙坦和 Ca 通道阻滞剂氨氯地平 3 个月。在基线和每个治疗期结束时测量血压、肾功能、血清 UA 水平和电解质。通过全基因组关联研究 (GWAS) 研究了与吲达帕胺治疗后 UA 升高相关的单核苷酸多态性 (SNP)。吲达帕胺显着降低办公室和家庭血压水平。吲达帕胺治疗也显着降低了估计的肾小球滤过率和血清钾，并增加了血清 UA。与 UA 升高较少（<1 mg/dl）的患者相比，UA 水平升高超过 1 mg/dl 的患者显示出显着更高的基线办公室 SBP 和血浆葡萄糖，并且肾功能下降幅度更大。鉴定出一些与吲达帕胺治疗后 UA 增加密切相关的 SNP。这项研究是关于 TD 治疗后 UA 升高相关 SNP 的第一份报告。

更新日期：2019-11-20

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